CIB4

Summary

CIB4 (calcium and integrin binding family member 4, HGNC:33703) is a protein-coding gene on chromosome 2p23.3, encoding Calcium and integrin-binding family member 4 (A0PJX0).

Enables calcium ion binding activity and magnesium ion binding activity.

Source: NCBI Gene 130106 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 29 total — 1 likely-pathogenic
• MANE Select transcript: NM_001029881

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33703
Approved symbol	CIB4
Name	calcium and integrin binding family member 4
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157884
Ensembl biotype	protein_coding
OMIM	610646
Entrez	130106

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000288861, ENST00000403670, ENST00000405346

RefSeq mRNA: 1 — MANE Select: NM_001029881 NM_001029881

CCDS: CCDS33160

Canonical transcript exons

ENST00000288861 — 7 exons

Exon	Start	End
ENSE00001299222	26640533	26640567
ENSE00001300075	26629410	26629506
ENSE00001315800	26641261	26641366
ENSE00001935797	26581205	26581393
ENSE00003553932	26595176	26595317
ENSE00003596697	26582825	26582913
ENSE00003683875	26583789	26583898

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 80.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0223 / max 19.3967, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27429	0.0167	3
27430	0.0057	3

Top tissues by expression

241 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	80.72	gold quality
right testis	UBERON:0004534	80.57	gold quality
right adrenal gland cortex	UBERON:0035827	78.10	gold quality
testis	UBERON:0000473	78.08	gold quality
right adrenal gland	UBERON:0001233	77.85	gold quality
left adrenal gland	UBERON:0001234	77.26	gold quality
left adrenal gland cortex	UBERON:0035825	75.97	gold quality
adrenal cortex	UBERON:0001235	73.90	gold quality
adrenal gland	UBERON:0002369	71.42	gold quality
ileal mucosa	UBERON:0000331	65.95	silver quality
right uterine tube	UBERON:0001302	65.00	gold quality
adult organism	UBERON:0007023	64.08	gold quality
right coronary artery	UBERON:0001625	59.90	gold quality
pancreatic ductal cell	CL:0002079	58.32	silver quality
oocyte	CL:0000023	56.44	gold quality
tibial artery	UBERON:0007610	55.82	gold quality
popliteal artery	UBERON:0002250	55.81	gold quality
right lung	UBERON:0002167	55.61	gold quality
deltoid	UBERON:0001476	55.47	gold quality
epithelial cell of pancreas	CL:0000083	54.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
left coronary artery	UBERON:0001626	54.03	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
coronary artery	UBERON:0001621	53.73	gold quality
left lobe of thyroid gland	UBERON:0001120	53.57	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
adrenal tissue	UBERON:0018303	53.31	gold quality
endocervix	UBERON:0000458	53.30	gold quality
thyroid gland	UBERON:0002046	53.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting CIB4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6724-5P	96.41	63.11	507

Literature-anchored findings (GeneRIF, showing 1)

• CIB4, as binding partners for the integrin alphaIIb subunit, which suggests that they are potentially involved in regulating integrin alphaIIb subunit activation. (PMID:22779914)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cib4	ENSMUSG00000053194
rattus_norvegicus	Cib4	ENSRNOG00000009898
drosophila_melanogaster	CG32812	FBGN0025642
drosophila_melanogaster	Cib2	FBGN0034558
drosophila_melanogaster	elm	FBGN0037358
drosophila_melanogaster	CG14362	FBGN0038186
caenorhabditis_elegans	calm-1	WBGENE00009260
caenorhabditis_elegans		WBGENE00014109
caenorhabditis_elegans		WBGENE00019108

Paralogs (8): TESC (ENSG00000088992), CIB2 (ENSG00000136425), CIB3 (ENSG00000141977), CHP2 (ENSG00000166869), CIB1 (ENSG00000185043), CHP1 (ENSG00000187446), PPP3R2 (ENSG00000188386), PPP3R1 (ENSG00000221823)

Protein

Protein identifiers

Calcium and integrin-binding family member 4 — A0PJX0 (reviewed: A0PJX0)

All UniProt accessions (1): A0PJX0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with ITGA2B (via C-terminus cytoplasmic tail region); the interaction is stabilized/increased in a calcium- and magnesium-dependent manner.

Miscellaneous. The binding of either calcium or magnesium may significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form).

RefSeq proteins (1): NP_001025052* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR051433	CIBP	Family

Pfam: PF13499

UniProt features (14 total): binding site 9, domain 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0PJX0-F1	90.07	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 156; 158; 163; 110; 112; 114; 121; 152; 154

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GOMF_MAGNESIUM_ION_BINDING, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NFE2L2.V2, TOP2B_TARGET_GENES, ZNF2_TARGET_GENES, MIR520G_5P, chr2p23, GSE14026_TH1_VS_TH17_DN, GSE14308_TH1_VS_INDUCED_TREG_DN, DESCARTES_FETAL_PLACENTA_SMOOTH_MUSCLE_CELLS, CC2D1A_TARGET_GENES, WRNIP1_TARGET_GENES, NOURUZI_NEPC_ASCL1_TARGETS, GSE2706_R848_VS_LPS_8H_STIM_DC_UP

GO Biological Process (0):

GO Molecular Function (4): magnesium ion binding (GO:0000287), calcium ion binding (GO:0005509), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	2
binding	1
cation binding	1

Protein interactions and networks

STRING

1464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIB4	SSMEM1	Q8WWF3	626
CIB4	TMC2	Q8TDI7	578
CIB4	SPEF2	Q9C093	527
CIB4	TSSK4	Q6SA08	519
CIB4	BPIFB6	Q8NFQ5	497
CIB4	WHRN	Q9P202	488
CIB4	CIB1	Q99828	470
CIB4	LRGUK	Q96M69	457
CIB4	TCF23	Q7RTU1	436
CIB4	FAM170B	A6NMN3	433
CIB4	FAM181B	A6NEQ2	432
CIB4	ALG14	Q96F25	420
CIB4	VCPIP1	Q96JH7	409
CIB4	KSR2	Q6VAB6	405
CIB4	BPIFB2	Q8N4F0	400

IntAct

26 interactions, top by confidence:

A	B	Type	Score
CIB4	UBB	psi-mi:“MI:0915”(physical association)	0.590
CIB4	TACO1	psi-mi:“MI:0915”(physical association)	0.560
CIB4	ZBTB9	psi-mi:“MI:0915”(physical association)	0.560
CIB4	TXN2	psi-mi:“MI:0915”(physical association)	0.560
CIB4	CREB5	psi-mi:“MI:0915”(physical association)	0.560
CIB4	VASN	psi-mi:“MI:0915”(physical association)	0.560
CIB4	ATG9A	psi-mi:“MI:0915”(physical association)	0.560
CIB4	MYPOP	psi-mi:“MI:0915”(physical association)	0.560
TACO1	CIB4	psi-mi:“MI:0915”(physical association)	0.000
ATG9A	CIB4	psi-mi:“MI:0915”(physical association)	0.000
MYPOP	CIB4	psi-mi:“MI:0915”(physical association)	0.000
ZBTB9	CIB4	psi-mi:“MI:0915”(physical association)	0.000
TXN2	CIB4	psi-mi:“MI:0915”(physical association)	0.000
CREB5	CIB4	psi-mi:“MI:0915”(physical association)	0.000
VASN	CIB4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): UBB (Affinity Capture-MS), ZNHIT2 (Affinity Capture-MS), UBB (Affinity Capture-MS), CIB4 (Two-hybrid), CIB4 (Two-hybrid), CIB4 (Two-hybrid), VASN (Two-hybrid), MYPOP (Two-hybrid), ATG9A (Two-hybrid), ZBTB9 (Two-hybrid), UBB (Affinity Capture-MS), CIB4 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX0, A1L1L6, A4IG32, B1A8Z2, B1H2N3, C7A278, D2HZB0, O88456, P04632, P06813, P07090, P22676, P47728, Q08331, Q0IIL1, Q17QE5, Q1RMX9, Q2HJF8, Q2KI69, Q32L26, Q32LU1, Q3T0E8, Q3ZBY3, Q4R518, Q5PPL2, Q5RDF9, Q5ZM73, Q6NVC5, Q6P6Q9, Q6P8Y1, Q6PHZ8, Q6PIL6, Q8BG51, Q8HYN7, Q8IXI2, Q8R426, Q8VCX5, Q8WWF8, Q99828, Q99MG9

Diamond homologs: A0PJX0, B1A8Z2, C7A276, C7A278, O75838, Q0IQB6, Q0IUU4, Q0P523, Q17QE5, Q3KQ77, Q568Z7, Q6PC72, Q96Q77, Q99828, Q9D9N5, Q9R010, Q9W2Q5, Q9Y6T7, Q9Z0F4, Q9Z309, G5EDN6, P28470, P63098, P63099, P63100, Q2TBI5, Q3HRN8, Q3HRN9, Q63810, Q63811, Q6CGE6, Q7XC27, Q96LZ3, Q9LTB8, O81223, O81445, P06707, P06708, P0CM54, P0CM55

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1176757	GRCh37/hg19 2p23.3-21(chr2:24881528-43460021)x3	Likely pathogenic

SpliceAI

1443 predictions. Top by Δscore:

Variant	Effect	Δscore
2:26582822:TACTT:T	donor_loss	1.0000
2:26582823:A:AC	donor_gain	1.0000
2:26582823:A:AT	donor_loss	1.0000
2:26582823:ACTT:A	donor_gain	1.0000
2:26582824:C:CT	donor_gain	1.0000
2:26582824:CTT:C	donor_gain	1.0000
2:26582824:CTTC:C	donor_gain	1.0000
2:26582826:T:TA	donor_gain	1.0000
2:26582912:ACCT:A	acceptor_loss	1.0000
2:26582914:C:CC	acceptor_gain	1.0000
2:26582918:C:CT	acceptor_gain	1.0000
2:26582928:C:CT	acceptor_gain	1.0000
2:26583785:ACAC:A	donor_loss	1.0000
2:26583786:CA:C	donor_gain	1.0000
2:26583787:A:AC	donor_gain	1.0000
2:26583788:C:CA	donor_gain	1.0000
2:26583788:CGTG:C	donor_gain	1.0000
2:26583894:AAAAT:A	acceptor_gain	1.0000
2:26583895:AAAT:A	acceptor_gain	1.0000
2:26583896:AAT:A	acceptor_gain	1.0000
2:26583896:AATCT:A	acceptor_loss	1.0000
2:26583897:AT:A	acceptor_gain	1.0000
2:26583898:TCTGC:T	acceptor_loss	1.0000
2:26583899:C:CC	acceptor_gain	1.0000
2:26583899:CTGC:C	acceptor_loss	1.0000
2:26583900:T:G	acceptor_loss	1.0000
2:26581390:GGAG:G	acceptor_gain	0.9900
2:26581393:GC:G	acceptor_loss	0.9900
2:26581394:C:CA	acceptor_loss	0.9900
2:26581394:C:CC	acceptor_gain	0.9900

AlphaMissense

1254 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:26595186:A:C	F106L	0.998
2:26595186:A:T	F106L	0.998
2:26595188:A:G	F106L	0.998
2:26595282:G:C	F74L	0.997
2:26595282:G:T	F74L	0.997
2:26595284:A:G	F74L	0.997
2:26582860:A:C	F164L	0.996
2:26582860:A:T	F164L	0.996
2:26582862:A:G	F164L	0.996
2:26595190:G:T	A105D	0.996
2:26595201:C:A	K101N	0.996
2:26595201:C:G	K101N	0.996
2:26595306:G:C	F66L	0.995
2:26595306:G:T	F66L	0.995
2:26595308:A:G	F66L	0.995
2:26595312:G:C	N64K	0.995
2:26595312:G:T	N64K	0.995
2:26629432:A:T	V55D	0.995
2:26640556:G:C	F22L	0.995
2:26640556:G:T	F22L	0.995
2:26640558:A:G	F22L	0.995
2:26582853:C:G	A167P	0.994
2:26582861:A:G	F164S	0.994
2:26583862:A:G	L122P	0.994
2:26595187:A:G	F106S	0.994
2:26595307:A:G	F66S	0.994
2:26581387:A:C	F178L	0.993
2:26581387:A:T	F178L	0.993
2:26581389:A:G	F178L	0.993
2:26595188:A:T	F106I	0.993

dbSNP variants (sampled 300 via entrez): RS1000019675 (2:26597363 C>T), RS1000043041 (2:26636220 G>A,C), RS1000053703 (2:26642048 C>G), RS1000063551 (2:26610002 G>A,C), RS1000136483 (2:26614736 G>T), RS1000171885 (2:26581276 A>T), RS1000240466 (2:26591885 A>G), RS1000301109 (2:26591670 A>G), RS1000312129 (2:26631087 C>A), RS1000312581 (2:26581795 C>A,T), RS1000413905 (2:26624025 C>T), RS1000422919 (2:26586997 A>G), RS1000435656 (2:26581092 T>C), RS1000448131 (2:26608494 G>T), RS1000460700 (2:26619428 T>C)

Disease associations

OMIM: gene MIM:610646 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001588_13	Periodontal microbiota	2.000000e-06
GCST003262_329	Post bronchodilator FEV1	3.000000e-06
GCST004495_22	BMI (adjusted for smoking behaviour)	8.000000e-08
GCST004495_23	BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004497_119	Body mass index (joint analysis main effects and smoking interaction)	6.000000e-08
GCST004497_120	Body mass index (joint analysis main effects and smoking interaction)	4.000000e-06
GCST004499_22	BMI in non-smokers	3.000000e-06
GCST004499_23	BMI in non-smokers	4.000000e-06
GCST006293_2	Response to olanzapine in schizophrenia	3.000000e-06
GCST007094_78	Diastolic blood pressure	1.000000e-27
GCST007095_66	Systolic blood pressure	1.000000e-21
GCST007095_67	Systolic blood pressure	8.000000e-20
GCST007096_182	Pulse pressure	2.000000e-15
GCST007097_149	Pulse pressure	4.000000e-06
GCST007097_150	Pulse pressure	9.000000e-07
GCST007098_117	Diastolic blood pressure	3.000000e-22
GCST007098_118	Diastolic blood pressure	2.000000e-20
GCST007099_235	Systolic blood pressure	4.000000e-33
GCST007429_64	Lung function (FVC)	4.000000e-11
GCST007431_33	Lung function (FEV1/FVC)	3.000000e-07
GCST008548_1	Fagerstrӧm test for nicotine dependence	3.000000e-07
GCST009734_6	Severe aplastic anemia	5.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004318	smoking behavior
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004312	vital capacity
EFO:0004713	FEV/FVC ratio
EFO:0009262	nicotine dependence symptom count
EFO:0006927	severe aplastic anemia

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Aflatoxin B1	increases methylation	2
propionaldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
Methapyrilene	increases methylation	1
Silicon Dioxide	decreases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.